Process for the preparation of optically active enones and intermediates thereof

Abstract

The present invention provides a simplified and convenient process for the preparation of an optically active enone such as 7,7-dimethyl-6,8-dioxabicyclo-[3,3,0]oct-3-en-2-one.The invention further provides novel optically active intermediate compounds.The process for the preparation of an optically active enone represented by the formula (4) comprises steps of (A) deprotecting the protecting group for the hydroxyl group at the 1-position in a compound represented by the formula (1) to a hydroxyl group (compound (2)), (B) oxidizing the hydroxyl group to a ketone group (compound (3)) and (C) deprotecting the protecting group for the hydroxyl group at the 4-position to form a double bond between the carbon atom at the 4-position and the carbon atom at the 5-position, according to the following reaction schemes:wherein R1 and R4 independently represent a cumyl group, alpha,alpha-diethylbenzyl, alpha,alpha-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, R2 and R3 jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R5 represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl group.

What is claimed is:  
     
       1. A process for the preparation of an optically active enone represented by the formula (4)                    
       wherein R 2  and R 3  jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R 5  represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl group, which comprises steps of 
       A) deprotecting the protecting group for the hydroxyl group at the 1-position in an optically active compound represented by the formula (1)                    
        wherein R 1  and R 4  independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, and R 2 , R 3  and R 5  are as defined above to form an optically active compound represented by the formula (2)                    
        wherein R 2 , R 3 , R 4  and R 5  are as defined above,  
       B) oxidizing the hydroxyl group at the 1-position in the compound (2) to form an optically active compound represented by the formula (3)                    
        wherein R 2 , R 3 , R 4  and R 5  are as defined above, and  
       C) deprotecting the protecting group for the hydroxyl group at the 4-position in the compound (3) to form a double bond between the carbon atom at the 4-position and the carbon atom at the 5-position.  
     
     
       2. A process for the preparation of an optically active enone represented by the formula (7)                    
       wherein R 2  and R 3  jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R 5  represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl group, which comprises steps of 
       A′) deprotecting the protecting group for the hydroxyl group at the 4-position in an optically active compound represented by the formula (1)                    
        wherein R 1  and R 4  independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, and R 2 , R 3  and R 5  are as defined above to form an optically active compound represented by the formula (5)                    
        wherein R 1 , R 2 , R 3  and R 5  are as defined above,  
       B′) oxidizing the hydroxyl group at the 4-position in the compound (5) to form an optically active compound represented by the formula (6)                    
        wherein R 1 , R 2 , R 3  and R 5  are as defined above, and  
       C′) deprotecting the protecting group for the hydroxyl group at the 1-position in the compound (6) to form a double bond between the carbon atom at the 1-position and the carbon atom at the 5-position.  
     
     
       3. An optically active compound represented by the formula (1)                    
       wherein R 1  and R 4  independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, R 2  and R 3  jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R 5  represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl group. 
     
     
       4. An optically active compound represented by the formula (2)                    
       wherein R 4  represents a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, R 2  and R 3  jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R 5  represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl, and its enantiomer represented by the formula (5)                    
       wherein R 1  represents a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, and R 2 , R 3  and R 5  are as defined above. 
     
     
       5. An optically active compound represented by the formula (3)                    
       wherein R 4  represents a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, R 2  and R 3  jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R 5  represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl, and its enantiomer represented by the formula (6)                    
       wherein R 1  represents a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, and R 2 , R 3  and R 5  are as defined above. 
     
     
       6. The process of  claim 1 , wherein R 2  and R 3  in formula (4) jointly represent acetonide. 
     
     
       7. The process of  claim 1 , wherein R 1  and R 4  in formula (1) each independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl or t-butyldimethylsilyl. 
     
     
       8. The process of  claim 1 , wherein R 5  in formula (4) is hydrogen atom or an alkyl group of 20 carbon atoms or less. 
     
     
       9. The process of  claim 2 , wherein R 2  and R 3  in formula (7) jointly represent acetonide. 
     
     
       10. The process of  claim 2 , wherein R 1  and R 4  in formula (1) each independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl or t-butyldimethylsilyl. 
     
     
       11. The process of  claim 2 , wherein R 5  in formula (7) is hydrogen atom or an alkyl group of 20 carbon atoms or less. 
     
     
       12. The compound of  claim 3 , wherein R 1  and R 4  in formula (1) each independently represent a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl or t-butyldimethylsilyl. 
     
     
       13. The compound of  claim 3 , wherein R 2  and R 3  in formula (1)jointly represent acetonide. 
     
     
       14. The compound of  claim 3 , wherein R 5  in formula (1) represents a hydrogen atom or an alkyl group of 20 carbon atoms or less. 
     
     
       15. The compound of  claim 4 , wherein R 4  in formula (2) represents a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl or t-butyldimethylsilyl. 
     
     
       16. The compound of  claim 4 , wherein R 2  and R 3  in formula (2) jointly represent acetonide. 
     
     
       17. The compound of  claim 5 , wherein R 4  in formula (3) represennts a cumyl group, α,α-diethylbenzyl, α,α-dimethyl-p-methoxybenzyl or t-butyldimethylsilyl. 
     
     
       18. The compound of  claim 5 , wherein R 2  and R 3  in formula (3) jointly represent acetonide.